The factors limiting regeneration after injury to the brain and spinal cord have not been defined. Effectiveness of peripheral nerve regeneration far exceeds central regeneration. However, outgrowth capacity following a lesion has been convincingly demonstrated in central monoamine fibers. We need to determine what conditions will enhance and optimize this regenerative growth and also facilitate functional recovery. Two hypotheses (that SIF cells or interneurons, can divide in an adult mammal, and that SIF cells can sprout and form new functional connections) will be tested directly to establish the extent and characteristics of responses of this catecholamine-rich component of sympathetic ganglia. In addition, two central aminergic model systems in which neurotoxin treatment appears to induce axonal remodelling will be studied in parallel. The bulbospinal monoamine system will be used to study (a) 5-HT and NE terminals in the spinal cord, (b) the question of synaptic connections being formed by new sprouts after neurotoxin treatment, and (c) possible regeneration and collateral sprouting in the transected spinal cord. Hypothesized enhancement substances will be tested for their ability to promote growth of aminergic axons across the transection site. The supraoptic commissure and paraventricular nucleus will be used to (a) test effects of neurotoxin-triggered response in neonatal, young adult, and aged animals and (b) obtain ultrastructural correlates of growth, elongation, synapse formation, and abortive growth. A combination of biostructure (EM; FM; morphometrics; adenylate cyclase histochemistry; HRP) and biochemistry (assays for cAMP, NE, 5-HT) will be used, with anticipation of neurophysiological and tissue culture correlations as later experimental stages warrant. This broad interdisciplinary approach is expected to provide related and coverging data to help in understanding the process of central and peripheral adrenergic plasticity.